PMC:1459172 / 25694-28666
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1459172","sourcedb":"PMC","sourceid":"1459172","source_url":"https://www.ncbi.nlm.nih.gov/pmc/1459172","text":"Implementation and performance\nThe algorithm is implemented in ANSI C, and is distributed as part of the of the Vienna RNA package. The resource requirements of RNAcofold and RNAfold are theoretically the same: both require (n3) CPU time and (n2) memory. In practice, however, keeping track of the cut makes the evaluation of the loop energies much more expensive and increases the CPU time requirements by an order of magnitude: RNAcofold takes about 22 minutes to cofold an about 3000 nt mRNA with a 20 nt miRNA on an Intel Pentium 4 (3.2 GHz), while RNAfold takes about 3 minutes to fold the concatenated molecule.\nThe base pairing probabilities are represented as a dot plot in which squares with an area proportional to Pij represent the the raw pairing probabilities, see Fig. 2. The dot plot is provided as Postscript file which is structured in such a way that the raw data can be easily recovered explicitly. RNAcofold also computes a table of monomer and dimer concentrations dependent on a set of user supplied initial conditions. This feature can readily be used to investigate the concentration dependence of RNA-RNA hybridization, see Fig. 3 for an example.\nFigure 2 Dot plot (left) and mfe structure representation (right) of the cofolding structure of the two RNA molecules AUGAAGAUGA (red) and CUGUCUGUCUUGAGACA (blue). Dot Plot: Upper right: Partition function. The area of the squares is proportional to the corresponding pair probabilities. Lower left: Minimum free energy structure. The two lines forming a cross indicate the cut point, intermolecular base pairs are depicted in the green upper right (partition function) and lower left (mfe) rectangle.\nFigure 3 Example for the concentration dependency for two mRNA-siRNA binding experiments. In [54], Schubert et al. designed several mRNAs with identical target sites for an siRNA si, which are located in different secondary structures. In variant A, the VR1 straight mRNA, the binding site is unpaired, while in the mutant mRNA VR1 HP5-11, A', only 11 bases remain unpaired. We assume an mRNA concentration of a = 10 nmol/1 for both experiments. Despite the similar binding pattern, the binding energies (ΔF = FAB - FA - FB) differ dramatically. In [54], the authors observed 10% expression for VR1 straight, and 30% expression for the HP5-11 mutant. Our calculation shows that even if siRNA is added in excess, a large fraction of the VR1 HP5-11 mRNA remains unbound. Like RNAfold, RNAcofold can be used to compute DNA dimers by replacing the RNA parameter set by a suitable set of DNA parameters. At present, the computation of DNA-RNA heterodimers is not supported. This would not only require a complete set of DNA-RNA parameters (stacking energies are available [49], but we are not aware of a complete set of loop energies) but also further complicate the evaluation of the loop energy contributions since pure RNA and pure DNA loops will have to be distinguished from mixed RNA-DNA loops.","divisions":[{"label":"title","span":{"begin":0,"end":30}},{"label":"p","span":{"begin":31,"end":617}},{"label":"p","span":{"begin":618,"end":1171}},{"label":"figure","span":{"begin":1172,"end":1675}},{"label":"label","span":{"begin":1172,"end":1180}},{"label":"caption","span":{"begin":1182,"end":1675}},{"label":"p","span":{"begin":1182,"end":1675}},{"label":"figure","span":{"begin":1676,"end":2445}},{"label":"label","span":{"begin":1676,"end":1684}},{"label":"caption","span":{"begin":1686,"end":2445}},{"label":"p","span":{"begin":1686,"end":2445}}],"tracks":[{"project":"2_test","denotations":[{"id":"16722605-12071944-1692568","span":{"begin":2745,"end":2747},"obj":"12071944"}],"attributes":[{"subj":"16722605-12071944-1692568","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93e2ec","default":true}]}]}}